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GENEWS ONLINE is the online edition of the official publication of The UPLB Genetics Society. The UPLB Genetics Society, also known as GeneSoc, is a duly recognized academic organization at UP Los Banos. The organization strives to promote and create awareness about the science of Genetics in the Philippines.

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From Nucleotides to Neurons: GeneSoc to feature the Human Brain in Genetics Week 2017

By: Sean Lemuel L. Santos (Hybrizyme)

With the theme, “Gene-Wired: Transcribing the Genetic Blueprint of the
Human Brain”, The UPLB Genetics Society will feature how genetics relate to the
study of the most complex organ in the body. From October 9-13, GeneSoc will
fire up neurons as it conducts the Genetics Week 2017 at the Wing C lobby of
the Institute of Biological Sciences in the University of the Philippines – Los
Banos. It will showcase in its exhibit a wide array of relevant topics that
delve deeper into the human brain through the lenses of genetics.

_______________________________________________________________

The brain is the most complex organ in the body. It controls our
sensations, allows us to speak, coordinates our movement, dictates when we will
sleep, and many others. But deep beneath the complexity of our biological
supercomputer lies the complexity of its genes. Like any other organ, the brain
is a product of an expressed information – the genes-in-action. The genes explain
how a baby brain develops into an adult one, what made the human brains evolve
from ancestral ones, why some are nocturnal while others are early-risers, etc.

Genes are a powerful tool in studying the information behind the human
brain. They are the blueprints of the brain’s architecture. By understanding
the genes, we begin to see the underlying mysteries of the human brain slowly
unfolding, revealing to us how all those neurons, chemicals, and hormones
packed inside the human ‘light-bulb’ originates from the stretches of our DNA.

Genetics and Neuroscience

The study of the brain in the light of genetics began in the mid-20th
century. It was Seymour Benzer, considered by many as the father of
neurogenetics, who started to develop the field in the early 1960s by studying
the brains of a fruit fly, Drosophila.
One of his early researches focused on how the genes affect our sleep-wake
cycle (California Institute of Technology, 2017). This cycle, also
called circadian rhythms, is partly controlled by the brain along with other
organs (Tortora & Derrickson, 2011).

Clock Genes

Decades after Benzer’s research, numerous studies about genes related to sleep
emerged. Recent studies have found out that there is such a thing as “clock
genes” – genes which affect our sleeping patterns. Scientists have discovered that
these clock genes are found in a part of the brain known as the suprachiasmatic
nucleus or SCN (Resnick, 2017) – the one that signals the pineal gland
to drug us to sleep (Tortora & Derrickson, 2011). These clock genes in
the SCN are repeatedly turned on and off in a 24-hour cycle, releasing proteins
when turned on and stops when turned off (Hastings, 1998). In other words, the
on-and-off cycle might be the reason why we have a sleep-and-wake cycle.

Brain Evolution

Sleep is a very essential activity both exhibited by us humans and our
chimp cousins. However, what sets us apart from other primates is our ability
to construct language. About a million years ago, early humans evolved to have
a larger neocortex, a part of the brain responsible for language. And the
reason for this could be partially attributed to a single change in the
sequence of DNA. Marta Florio of the Harvard Medical School and her colleagues
in Germany studied a gene called ARHGAP11B found in Neanderthals and Denisovans
but not in chimpanzees. They found out that this gene multiplies ‘immature’ cells
that would later become the neurons of the brain. The ancestor of the gene, the
ARHGAP11A on the other hand, is the one found in chimpanzees and cannot do what
the former does. Florio and her colleagues discovered that the ARHGAP11B gene can
be turned to look like the ARHGAP11A gene by changing a single base (C into G)
in the sequence. And when this happens, the ability of the ARHGAP11B gene to
multiply immature cells was lost (Batsakis, 2016). This implies that the evolution of a
larger brain was significantly influenced by even a single substitution of a base.

Epigenetics of Stress

When it comes to our brain’s stress response, genetics also play a key
role. In one study of animal behavior, researchers have observed that rats with
nurturing mothers tend to become less susceptible to stressors whereas those
rats with negligent mothers tend to become the opposite. The reason for this is
that, when the rats were nurtured, the genes which respond to stress become
inactivated - an example of epigenetic
changes or changes in which genes are turned on without necessarily
changing the DNA. These epigenetic changes are reversible, meaning that the
more sensitive rats could become less sensitive to stress when their negligent
mothers are swapped with nurturing ones. Moreover, these epigenetic changes can
be passed down to succeeding generations (University of Cambridge, 2017).

Predisposed Addiction

Addiction was once believed as a person’s own sinful decision. But
recently, science has shown that addiction is not just personal and
environmental but is also highly influenced by our genes. For instance,
researchers have found out that a variant allele in the DRD2 gene (gene that codes for dopamine receptor) is more common in
alcoholic and cocaine-addicted people. On the other, in another study using
mice, it was discovered that those mice without the Htr1b gene (gene for serotonin receptor) tend to be more addicted
to alcohol and cocaine (Genetic Science Learning Center, 2013)

The Aging Brain

Genes also affect brain aging. In a study done by researchers at the
Columbia University Medical Center, it was found out that a gene called TMEM106B affects the aging of a brain region called frontal
cortex. The frontal cortex is the one located in the frontal lobe and is responsible
for higher cognitive functions (Tortora & Derrickson, 2011).In a group of people aged 65 and above, those that
have two ‘bad’ copies of the TMEM106B
gene have a frontal cortex that looks 12 years older than those with two ‘good’
copies of the gene. When a person reaches 65 and has two ‘bad’ copies,
his/her brain responds badly to stressors and ages hastily. The opposite occurs
in a person with two ‘good’ copies. The study
published in Cell Systems also noted
that this TMEM106B gene could be
responsible for the onset of a certain type of dementia (Columbia University Medical Center, 2017).

Alzheimer’s Disease

As we age, there are numerous diseases that our brain could suffer from.
One of them is Alzheimer’s disease. Characterized mainly by the loss of
short-term memory, Alzheimer’s disease or simply AD is a brain disease that could
also be traced in our DNA. According to the National Institutes of Health of
the U.S., there is a gene called APOE which
contribute to the development AD. The APOE
gene has at least three different variants (alleles) namely: E2, E3, and E4. The APOE E4 allele is
the one which has been linked to AD. People who have one copy of this allele have
a high risk of developing AD. Meanwhile, those which have two copies are at a
higher risk for AD onset. This E4
allele is linked to the accumulation of plaques in the brain tissue which could
result to the death of brain cells and the beginnings of AD (National Institutes of Health, 2017).

Neuroimaging

To better understand neurodegenerative diseases like Alzheimer’s, the
brain must be examined by looking into its structure. This is where an emerging
technology called Neuroimaging Genetics comes into play. In Neuroimaging
Genetics, the data from brain images are correlated with the data from the DNA.
In other words, the phenotype (the brain) is associated with the genotype. And
since people have varied genotypes, scientists can then begin to point out
which of those might be causing a particular change in the brain. Surprisingly,
there have been instances where even only a single change in the DNA sequence
caused a huge difference in the structure of the brain (Bigos, Hariri, & Weinberger, 2016).

Intelligence Genes

If our brains become less intelligent as we age, could we possibly reverse
the process? The answer to this is yes, at least genetically. In 1999,
scientists at the Princeton University tried to genetically improve
intelligence by inserting a gene called NR2B
in mice named “Doogie”. This NR2B gene
excites the receptors in the hippocampus, a region of the brain responsible for
memory (Tortora & Derrickson, 2011). As a result of the
gene’s action, the mice showed better memory and more improved learning
abilities. More interestingly, these mice were able to retain their
intelligence unlike other mice which displayed a decline in their mental
abilities (Radford, 1999).

Genes and the human brain are inseparable. The brain, being the most
complex of all the organs, are traceable in the most complex biomolecule, the
DNA. The genetics of the human brain reveal a deeper understanding of the
brain’s development, its evolutionary history, its diseases, how it ages, and
how it can be cured. And knowing this, it can surely be said that the human
brain is a gene-wired architecture of nature.

The DNA Backbone

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About The UPLB Genetics Society

The UPLB Genetics Society, also known as GeneSoc, is a duly recognized academic organization in UPLB that was established in 1983. Through the years, the organization strives to promote and create awareness about the science of Genetics in the Philippines.